The FDA-approved drug irbesartan inhibits HBV-infection in HepG2 cells stably expressing sodium taurocholate co-transporting polypeptide

Abstract

Background: Little is known about the early steps of the HBV life cycle due to the lack of susceptible cells permissive for viral infection. Hence, viral entry has not been exploited for antiviral targets, but the recent seminal discovery of sodium taurocholate co-transporting polypeptide (NTCP) as the cellular receptor for HBV entry opened up many avenues of investigation, making HBV entry amenable to therapeutic intervention. Methods: In order to exploit HBV entry, we established a HepG2-NTCP cell line that supports HBV infection. Over 70% of cells were infected at a dose of 104 genome equivalents (GEq) per cell. Several FDA-approved drugs with NTCP-inhibiting activity were tested for their ability to inhibit HBV infection of the cell line. Results: Consistent with their NTCP inhibitory activities, our results showed that several of them inhibit HBV infection. In particular, irbesartan, a drug used for the treatment of hypertension, inhibits HBV infection at the 50% effective concentration value of 35 μM. Conclusions: The observation that the pharmacological inhibitors of the NTCP transporter could block HBV entry suggests that NTCP represents an attractive molecular target for therapeutic intervention in HBV infection.